1. Field of the Invention
The present invention relates to novel biologically active polypeptides, more particularly, artificially created polypeptides which are commonly capable of inducing the production of interferon-gamma (hereinafter abbreviated as “IFN-γ”) by immunocompetent cells.
2. Description of the Prior Art
The present inventors successfully isolated some polypeptides which are capable of inducing the production of IFN-γ by immunocompetent cells, as well as cloned cDNAs which encode the polypeptides (hereinafter called “the wild-type polypeptides”); the relating inventions are disclosed in Japanese Patent Kokai Nos. 27,189/96 and 193,098/96 and Japanese Patent Application No. 67,434/96. It is known that the wild-type polypeptides usually contain SEQ ID NOs:1–3 as consensus partial amino acid sequences, and that they usually possess properties of inducing the formation of killer cells and enhancing their cytotoxicities, in addition to the property of inducing production of IFN-γ, a useful biologically active protein. Because of the properties, the use of the wild-type polypeptides as antiviral, antimicrobial, antitumor, and/or anti-immunopathic agents, etc. is in great expectation.
However, as described in Japanese Patent Application No. 67,434/96 by the present applicant, there is the problem that natural cells commonly do not enable producing the wild-type polypeptide in desired amounts. The present inventors energetically investigated the cause, revealing that the wild-type polypeptides usually exist in the form of precursor exhibiting no biological activity in natural cells. The precursor has been proved to be converted into an active form by the action of converting enzymes such as interleukin-1β converting enzymes, which is described in Japanese Patent Application Nos. 207,691/96 and 213,267/96 by the present applicant.
The wild-type polypeptides are probably instable, which would be involved in the above problem as another cause. Progress in recombinant DNA techniques of recent years have facilitated to remove and/or replace one or more amino acids in biologically active proteins to develop mutagenized polypeptides. However, even the progressed recombinant DNA techniques couldn't improve the stability of every protein with the inherent activity, unless taking trails and errors on the proteins individually.